Anticipation in inflammatory bowel disease: A phenomenon caused by an accumulation of confounders

Inflammatory bowel disease (IBD) has a definite genetic component as docume nted by epidemiological and linkage evidence. It shows an earlier onset of disease in children of affected patients than in their parents. This has le ad to speculations about genetic anticipation in this disorder. 2,007 IBD p atients with sporadic disease and 472 multiplex familial cases (including 1 03 affected parents and 99 children of affected patients) were evaluated wi th a multi-item questionnaire as part of a study of inflammatory bowel dise ase genetics. The Mann-Whitney U-test and the general linear model were use d for analysis. Clinical characteristics such as presence of fistulae, sten oses, extraintestinal manifestations, and other parameters, which are relat ed to the severity of the disease, were found to be similar between familia l and sporadic cases of IBD (corrected P greater than or equal to 0.31 for all tests). The mean-age-of onset in children of affected patients was 19.4 years earlier than in their parents. However, the age of the parental coho rt was significantly higher (27 years) and the diagnostic interval also lon ger (1.7 years). If these confounders are corrected in a general linear mod el, no significant difference is evident for the age-of-onset between the g roups (P greater than or equal to 0,52), There is no evidence for genetic a nticipation in inflammatory bowel disease. The absence of genetic anticipat ion is consistent with the clinical similarity of familial and sporadic inf lammatory bowel disease. This finding justifies the primary genetic analysi s of familial disease under the assumption that their genetic background wi ll be representative for all presentations of IBD, Am. J, Med. Genet, 92:17 8-183, 2000, (C) 2000 Wiley-Liss, Inc.